Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium-Calpain-Caspase 7-PARP Pathway
Cordycepin Induces Apoptosis of CGTH W-2 Thyroid Carcinoma Cells through the Calcium-Calpain-Caspase 7-PARP Pathway
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DOI：
10.1021/jf1028976
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发表时间：
2010-11-24
影响因子：
6.1
通讯作者：
Wang, Seu-Mei
中科院分区：
文献类型：
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作者：
Chen, Ying;Chen, Yung-Chia;Wang, Seu-Mei
虫草素是从冬虫夏草中分离的一种核苷，是一种多聚腺苷酸化抑制剂，具有抗肿瘤作用。本实验以甲状腺滤泡癌细胞系CGTH W-2为研究对象，探讨虫草素抗肿瘤作用的机制。虫草素降低细胞活力，导致凋亡，但不坏死。虫草素增加细胞内钙水平，触发钙蛋白酶激活，导致细胞凋亡。BAPTA/AM和calpeptin抑制虫草素诱导的caspase 7和聚（ADP-核糖）聚合酶（PARP）的切割，这意味着钙和calpain的上游作用。CGTH W-2细胞表达四种腺苷受体亚型：A（1）AR、A（2A）AR、A（2B）AR和A（3）AR。AR亚型特异性拮抗剂均不同程度地阻断虫草素诱导的细胞凋亡。A（1）AR和A（3）AR的小干扰RNA阻断虫草素诱导的细胞凋亡。结论：虫草素诱导CGTH W-2细胞凋亡是通过Ca 2 +-calpain-caspase 7-PARP途径介导的，AR参与了虫草素诱导CGTH W-2细胞凋亡的作用。
Cordycepin, a nucleoside isolated from Cordyceps sinensis, is an inhibitor of polyadenylation and has an antitumor effect. We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mechanism of the anticancer effect of cordycepin. Cordycepin decreased cell viability and resulted in apoptosis but not necrosis. Cordycepin increased intracellular calcium levels triggering calpain activation, which led to apoptosis. BAPTA/AM and calpeptin inhibited the cordycepin-induced cleavage of caspase 7 and poly (ADP-ribose) polymerase (PARP), implying an upstream role of calcium and calpain. CGTH W-2 cells expressed four subtypes of adenosine receptors (AR), A(1)AR, A(2A)AR, A(2B)AR, and A(3)AR. Specific antagonists to AR subtypes all blocked cordycepin-induced apoptosis to different degrees. Small interfering RNA for A(1)AR and A(3)AR abrogated cordycepin-induced apoptosis. In conclusion, the cordycepin-induced apoptosis of CGTH W-2 cells is mediated by the calcium-calpain-caspase 7-PARP pathway, and ARs are involved in the apoptotic effect of cordycepin.